Field of the Disclosure
The present disclosure relates generally to pharmaceutical compositions, and more particularly, to natural suspending agents that improve stability in oral pharmaceutical suspensions.
Background Information
Some drugs are insoluble in all acceptable media and must, therefore, be administered as a tablet, capsule, or as a suspension. In some situations, suspensions possess certain advantages over other dosage forms. Because of their liquid character, suspensions represent an ideal dosage form for patients who have difficulty swallowing tablets or capsules. This factor is of particular importance in the administration of drugs to children and elderly persons. Additionally, suspensions of insoluble drugs can also be used externally, often as protective agents.
One challenge of suspension formulation is sedimentation, caking, distribution, and re-suspension of the solid particles. A suspension should not settle rapidly and it should be sufficiently fluid to flow easily under the conditions of administration. Because suspensions are energetically unstable, the particles that have settled tend to interact to form a cake or hard crystalline network. To prevent this, suspensions are formulated such that caking is minimized so particles that have settled can be readily re-dispersed upon shaking.
Pharmaceutical suspensions consist of solid particles of variable sizes dispersed in a liquid medium, generally an aqueous solution. Typically, pharmaceutical suspensions include a suspending agent that helps the active pharmaceutical ingredients (APIs) stay suspended in the liquid medium, thereby reducing caking at the bottom of the suspension. Consistency of the solid particles throughout the suspending medium is facilitated with the API as solid particles staying suspended in the continuous phase, thereby allowing consistent withdrawal of uniform doses. One of the properties of a well-formulated suspension is that it should easily be re-suspended by the use of moderate agitation. A good suspension should allow the withdrawal of uniform and accurate doses throughout the period of medication.
Konjac glucomannan powder, which may be used as a suspending agent, is a pure natural, odorless soluble fiber that is produced from the Konjac plant. Konjac powder does not include protein, fat, sugar or starch. Konjac powder is also gluten free and wheat free, and does not have any calories. Konjac powder can be used as a thickening agent in many applications, such as, for example in food, drinks, pharmaceuticals, cosmetics, and the like. It has about ten times the thickening power of cornstarch. Additionally, Konjac powder does not thicken very much when mixed with cold water, but quickly thickens when it is heated.
Xanthan gum is widely used in cosmetics and personal care industry as a rheology control agent for aqueous systems. However, currently available Xanthan gum needs to be improved to enhance its properties, broaden its applications, and provide functionality at a lower cost.
Oral dosage forms have stability problems associated with maintaining the APIs in suspension. Stability problems include sedimentation, creaming, crystal growth (agglomeration), separation and difficulty to re-disperse to obtain original suspensions. Many oral pharmaceutical suspensions enable the APIs to settle out as sediment or creaming to the surface, thereby having variations in the therapeutic concentration of APIs within the suspension. This results in under dosing or over dosing of the patient, which may seriously compromise the patient's recovery.
Additionally, oral pharmaceutical suspensions should be readily pourable so that the dose is easy to administer. The requirement that oral pharmaceutical suspensions be readily pourable effectively places an upper limit on the viscosity of the suspensions. This restriction also limits the amount of APIs that the overall composition will suspend. Moreover, it has been shown that the type of suspending agents rather than the physical characteristics of the APIs appear to have the main influence on the physical stability of suspensions.